PB2008: INCIDENCE OF DRUG-INDUCED MYELOSUPPRESSION AND ASSOCIATED ADVERSE EVENTS, QUALITY OF LIFE, AND MEDICAL RESOURCE USE IN MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA
Authors: Maria Vutcovici Nicolae, Mei Dong, Teraneh Z. Jhaveri, Laura De Benedetti, Hanane Khoury, Lee Stern, Mellissa Williamson, Jason Beal, Matthew Radford, Mindy Chen, Siu-Chi Chang Sun, Evelyn Rustia, Mathias Schulz, Giri Ramsingh, Eduardo Sabate
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: Adverse events (AEs) associated with drug-induced myelosuppression are of substantial concern when treating patients with hematologic malignancies, especially with combination therapies. Aims: This study aimed to provide a comprehensive overview of the evidence available on drug-induced myelosuppression in patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Methods: A systematic literature review (SLR) was conducted using MEDLINE, Embase, and Cochrane to identify studies published in 2002-2022, explicitly targeting drug-induced myelosuppression with current and emerging treatments for MDS and/or AML (venetoclax [VEN], azacitidine [AZA], magrolimab, sabatolimab, decitabine [DEC], cedazuridine, lenalidomide [LEN], low-dose cytarabine [LDAC], intensive chemotherapy [IC]) in terms of drug-induced AEs, treatment discontinuation, quality of life (QOL), and medical resource use (MRU). Articles were selected based on predefined eligibility criteria (PICO+ framework), with a focus on specific countries (US, UK, Spain, Italy, France, Germany). Results: A total of 48 studies reporting on VEN-, AZA-, DEC-, LEN-, LDAC-, and IC-based regimens met the inclusion criteria. In MDS populations, myelotoxicity associated with AZA, DEC, and LEN monotherapies was reported in all blood cell lineages. In AML populations, myelosuppression associated with all regimens except LEN was reported in all blood cell lineages. In general, the reported incidence of myelosuppressive AEs was higher in studies published prior to 2010 vs more recently (2018-2022) and in studies in patients with AML or MDS who had received prior treatment vs treatment-naive patients. Differences between the two time periods might be explained by improved supportive care (AE prophylaxis and management). In treatment-naive AML populations, the incidence of any-grade febrile neutropenia, leukopenia, and anemia was up to 3-fold higher with AZA combination therapy vs monotherapy, and the incidence of any-grade neutropenia and febrile neutropenia was 2-fold higher with LDAC combination regimens vs monotherapy, suggesting an additive effect. The most common reasons for treatment discontinuation were AEs and disease progression. QOL was significantly improved with AZA monotherapy; however, hematologic improvement was not explicitly mentioned as the main driver. There were no data on combination therapies to indicate whether the improvement in QOL compensated for the added drug-induced AEs. The few studies that reported on the impact of myelosuppression on MRU did not provide conclusive results. Summary/Conclusion: This SLR suggests that combining ≥2 myelosuppressive drugs may result in increased toxicity; however, the lack of evidence on the impact of myelotoxicity on QOL and MRU with ≥2 myelosuppressive drugs limits informed decision-making in routine clinical practice. Further research is needed to explore the impact of drug-induced myelosuppression in patients with MDS or AML. Keywords: Systematic review, MDS/AML, Myelosuppression